ALX148: Designed For Safety To Maximize Efficacy

Jaume Pons, Ph.D, Founder, President and CEO of ALX Oncology

CD47|SIRPα Summit

November 4, 2020

ALX Oncology

DISCLAIMER

1

This presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation, including without limitation, statements regarding our future results of operations and financial position, business strategy, product candidates, planned preclinical studies and clinical trials, results of clinical trials, research and development costs, regulatory approvals, timing and likelihood of success, as well as plans and objectives of management for future operations are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “would,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “believe,” “estimate,” “predict,” “potential,” or “continue” or the negative of these terms or other similar expressions.

We have based these forward-looking statements largely on our current expectations and projections about our business, the industry in which we operate and financial trends that we believe may affect our business, financial condition, results of operations and prospects and these forward-looking statements are not guarantees of future performance or development. These forward-looking statements speak only as of the date of this presentation and are subject to a number of risks, uncertainties and assumptions, including, among other things: our history of incurring significant net losses since our inception and our expectation that we will continue to incur significant net losses for the foreseeable future; sufficiency of our cash and cash equivalents to fund our planned operations; the need for additional capital to finance our operations and our ability to obtain such financing, if at all, on terms that are favorable to us; our limited operating history and absence of products approved for commercial sale; our substantial dependency on the success of our lead product candidate, ALX148, which is in clinical development and which has not completed a pivotal trial; the fact that outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials, and the results of our clinical trials may not satisfy the requirements of the Food and Drug Administration (“FDA”) or other comparable foreign regulatory authorities; the possibility that our product candidates may cause significant adverse events or other undesirable side effects when used alone or in combination with other treatments; the fact that the clinical trials of our product candidates are expensive, time consuming and difficult to design and implement and may fail to demonstrate adequate safety, efficacy and potency of our product candidates or provide the basis for marketing approval; the lengthy, time-consuming and inherently unpredictable nature of the regulatory approval processes of the FDA and comparable foreign regulatory authorities, which could lead to our inability to generate product revenue; our ability to obtain, maintain and enforce patent protection and other intellectual property for our product candidates and related technology; our dependency on our key personnel and our ability to successfully attract, motivate and retain highly qualified personnel; the fact that our preclinical research is conducted solely by Tallac Therapeutics, Inc. (“TallacTherapeutics”) and that we are dependent on Tallac Therapeutics to perform its contractual research obligations on an effective or timely basis; the potential adverse impact of COVID-19 on our business, including our ongoing and planned clinical trials and preclinical research; and material weaknesses in our internal control over financial reporting.

New risk factors emerge from time to time and it is not possible for our management to predict all risk factors, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in, or implied by, any forward-looking statements.

Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified, you should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Information regarding additional risks and uncertainties may be found in our Quarterly Report on Form 10-Q filed with the U.S. Securities and Exchange Commission (“SEC”) on August 27, 2020 and our future reports to be filed with the SEC. Except as required by applicable law, we undertake no obligation to update publicly any forward-looking statements for any reason after the date of this presentation.

In addition, statements that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this presentation, and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and you are cautioned not to unduly rely upon these statements.

This presentation concerns drugs that are under clinical investigation and which have not yet been approved for marketing by the FDA. It is currently limited by federal law to investigational use, and no representation is made as to its safety or effectiveness for the purposes for which it is being investigated.

This presentation also contains estimates and other statistical data based on independent industry publications or other publicly available information, as well as other information based on our internal sources. We have not independently verified the accuracy or completeness of data contained in these industry publications and other publicly available information. Accordingly, we make no representations as to the accuracy or completeness of that data and you are cautioned not to give undue weight to such estimates.

ALX Oncology

OVERVIEW

Lead product candidate, ALX148

CD47 blocker

• Designed for use in combination

• Tolerability profile enables higher dosing

• Higher dosing may enable greater efficacy

Clinical proof-of-principle in both hematologic and

solid tumors

Initial focus on MDS, AML and solid tumors

2

ALX Oncology (Nasdaq: ALXO) is a clinical-

stage immuno-oncology company focused

on helping patients fight cancer by

developing therapies that block the CD47

checkpoint pathway and bridge the innate

and adaptive immune system

ALX Oncology

CD47: TUMOR ASSOCIATED ANTIGEN (TAA)- MYELOID CHECKPOINT DUALITY

TAA-Expression levels on cancer and normal cells

3

Checkpoint Mechanism: “do not eat me”

Macrophage

Cancer cell

CD47SIRPα

Don't eat me

Eat me

Anti-cancer drug

Fc receptor

ALX Oncology

CD47 RNA EXPRESSION ACROSS NORMAL TISSUES

4

Using CD47 directly targeting cancer cells as TAA will be limited by on-target off-tissue toxicity

ALX Oncology

TARGETING CD47 AS TUMOR ASSOCIATED ANTIGEN

5

Macrophage

Cancer cell

Anti-CD47

SIRPα

Fc receptor

Red blood cell Anti-cancer

drug

CD47

Anti CD47 with active Fcdirectly targets cancer cells

But also targets normal cells

Dose limitations prevent full blockade of CD47 and active fc competes with combo drug

ALX Oncology

TARGETING CD47 AS CHECKPOINT: ALX ONCOLOGY’S APPROACH

6

Cancer cell

CD47

TAA

ALX148ALX148

Macrophage

SIRPα

Fc receptor

Inactive Fc

Anti-cancer drug

Red blood cell

ALX148

Anti CD47 with inactive Fc binds and block CD47-Sirpa interaction

It spares normal cells

High dose allows full blockade of CD47 and

maximizes activity of combo drug

ALX Oncology

AFFINITY TO CD47 AND FCg RECEPTORS

7

Research tools

*molecules produced at ALX Oncology, based on public information

KD measured by SPR at ALX Oncology

CD47 binding domains

Fc domain

Fc Domain CD16a (KD nM)

CD32a(KD nM)

CD32b/c(KD nM)

CD64(KD nM)

IgG1 370 400 2000 0.004

IgG4 S228P 3000 810 850 1

IgG1 DEAD NB NB NB NB

Name Fc Domain (Human)

KD human CD47 (nM)

KD mouse CD47 (nM)

Effector function

ALX148 IgG1 DEAD 0.14 9 -

ALX216 IgG4 S228P 0.14 9 ++

ALX377 IgG1 wt 0.14 9 ++++

ALX126 IgG1 DEAD 3 65 -

5F9 (magrolimab)* IgG4 S228P 7 NB ++

TTI-621* IgG1 wt 500 NB ++++

TTI-622* IgG4 S228P 500 NB ++

ALX Oncology

SINGLE AGENT: INCREASE EFFECTOR FUNCTION ENHANCES PHAGOCYTOSIS

8

SINGLE

10-2 10-1 100 101 102 10300

5

10

15

20

nM

% C

FS

E

NP Don405 single p1ALX148

Active IgG1 Control

media only

ALX216 (IgG4)

ALX377 (IgG1)

All molecules with same high affinity CD47 binding domain (KD 140 pM)

DLD1 cancer cells

ALX Oncology 9

Inactive Fc is the core

determinant of safety

profile

CD-1 mice received 30 mg/kg IV single dose

****p<0.0001, ***p<0.001

SINGLE AGENT: INCREASED EFFECTOR FUNCTION INCREASES CYTOPENIAS

All molecules with same high affinity CD47 binding domain (KD 9 nM for MOUSE CD47)

ALX Oncology

SINGLE AGENT: INCREASE OF CD47 AFFINITY ENHANCES PHAGOCYTOSIS

10

SINGLE

CD47 as TAA does not require 100% receptor occupancy, but there is higher activity at higher occupancy

All molecules with same effector function (IgG4)

KD nM

0.14

7

500

0.01 0.1 1 10 100 100000

10

20

30

nM

% C

FS

E

NP Don406 single (All IgG4)

TTI-622

5F9

ALX216 (IgG4)

Active IgG1 Control

media only

0.00

01

0.00

10.

01 0.1 1 10 10

0

10000

0

20

40

60

80

100

120

nM

Perc

en

t C

D47 O

ccu

pan

cy

CD47 Occupancy

ALX148

5F9

TTI-621

TTI-622

0.5 1.0 1.5 2.0 2.5

-20

0

20

40

60

80

100

% In

hib

itio

n

% Inhibition of SIRPa Signaling

DIscoverX PathHunter SIRPa Signaling Bioassay

ALX148

TTI-621

TTI-622

5F9

ng/ml

EC50s ng/ml :

ALX148 25.15F9 74.4TTI-621 > 150 TTI-622 > 150

DLD1 cancer cells

ALX Oncology

COMBINATION: ACTIVE FC DOES NOT ENHANCE ANTICANCER ANTIBODY

11

COMBO

DLD1 cancer cellsCetuximab: 100ng/mL

High affinity and no effector function maximizes the phagocytosis of combo drug in vitro

ALX Oncology

CD47 AS CHECKPOINT: HIGH AFFINITY IS REQUIRED TO INHIBIT CELL/CELL INTERACTION

12

100% inhibition is achieved at near complete receptor occupancy level

0.00

01

0.00

10.

01 0.1 1 10 10

0

10000

0

20

40

60

80

100

120

nM

Perc

en

t C

D47 O

ccu

pan

cy

CD47 Occupancy

ALX148

5F9

TTI-621

TTI-622

SIGNALING

ALX Oncology

CD47-SIRPa INTERACTION INHIBIT DENDRITIC CELLS IN TUMOR MICROENVIRONMENT

13

T cell

Den

dri

tic

cell

CD47

SIRPα

SIRPα

Cancer cell

T cell

T cell

Den

dri

tic

cell

Den

dri

tic

cell

CD47

TCR

SIRPα

Tumor antigen

Tumor antigen

ALX148

Cancer cell Cancer cell

CD47-Sirpa interaction inhibits Dendritic cells and keep macrophages in M2 phenotype

Blockade of CD47 activate DCs

Activated DC present antigens to T-cells and these get activated and

attack cancer cells

ALX Oncology

CD47 AS CP: HIGH AFFINITY IS REQUIRED TO DEREPRESS DC IN VIVO

14

In VIVO

ALX

148

with

lower

affin

ityPBS

0

250

500

750

1000

Med

ian

Flu

ore

scen

t In

ten

sit

y (

MF

I) 3 mpk CD8- DC CD86

ALX

148

with

lower

affin

ityPBS

0

200

400

600

800

1000

Med

ian

Flu

ore

scen

t In

ten

sit

y (

MF

I) 3 mpk CD8 DC CD86

mCD47:ALX148 = KD 9 nMALX126 = KD 65 nM

3 mpk ALX148 or ALX126

Harvest Spleen

I.P.

3.5hrs

Measure activation of DCs by flow cytometry

ALX Oncology

ALX148: METICULOUSLY DESIGNED CD47 BLOCKER

15

High affinity CD47 binding

domain of SIRPα

High affinity CD47 binding

domains of SIRPα

Inactive Fc

domainPresence of Fc domain ensures slow

clearance and long half-life

Inactive Fc domain eliminates

binding activity

No dose dependent

cytopenia

Potently blocks CD47

signal on cancer cells

Less frequent

dosing

Designed for safety

and efficacy

• ~Half the molecular weight of an antibody

• Increases solid tumor penetration

• Standard antibody manufacturing process

ALX Oncology

PIPELINE: COMBINATION TRIALS WITH ALX148

16

>150 patients dosedwith ALX148since 2017

Indication IND filingpreparation

INDsubmitted

Phase 1 Phase 2 Phase 3 Fast track

SOLI

D T

UM

OR

S

HNSCCHead And Neck

Squamous Cell

Carcinoma

GCGastric/

Gastroesophageal

Junction Cancer

HEM

ATO

LOG

Y

MDSMyelodysplastic

Syndromes

AMLAcute Myeloid Leukemia

NHLNon-Hodgkin’s

Lymphoma

Herceptn

azacitidine

Rituximab

Keytruda+ 5FU + platinum

azacitidine + venetoclax

Herceptin+ Cyramza + paclitaxel

Keytruda

Herceptin

ALX Oncology

ALX148 DEMONSTRATES CONSISTENT TOLERABILITY PROFILE

Treatment relatedadverse events

ALX148+ Rituxan (N=33)

ALX148+ Keytruda (N=52)

ALX148+ Herceptin (N=30)

Total n (%) Grade 3 Total n (%) Grade 3 Total n (%) Grade 3

Fatigue 3 (9.1%) - 6 (11.5%) - 9 (30.0%) -

Rash 6 (18.2%) - 5 (9.6%) - - -

AST increased - - 9 (17.3%) - - -

Platelets decreased - - 4 (7.7%) 2 (3.8%) 5 (16.7%) 2 (6.7%)

ALT increased - - 7 (13.5%) 1 (1.9%) - -

Pruritus - - 5 (9.6%) - 3 (10.0%) -

Pyrexia - - 3 (5.8%) - 3 (10.0%) -

Decreased appetite - - 2 (3.8%) - 3 (10.0%) -

Anemia 2 (6.1%) 1 (3.0%) 5 (9.6%) 1 (1.9%) 2 (6.7%) -

Infusion reaction - - 4 (7.7%) - - -

Neutropenia / Neutrophil count decr 2 (6.1%) 2 (6.1%) 2 (3.8%) 1 (1.9%) 2 (6.7%) 2 (6.7%)

Nausea 2 (6.1%) - 2 (3.8%) - 2 (6.7%) -

Alkaline phosphatase incr - - 3 (5.8%) - - -

Arthralgia - - 3 (5.8%) - - -

WBC decreased - - 3 (5.8%) - - -

Myalgia - - 2 (3.8%) - - -

Tolerability profile

may enable broad

combination potential

Treatment related adverse events occurring in 2 subjects in all histologies at 10 & 15 mg/kg QW.

Data Cutoff 1 April 2020. 17

ALX Oncology

ALX148 CLINICAL PHARMACOKINETICS AND CD47 TARGET OCCUPANCY

18

• Steady-state half-life of ALX148 at 10 mg/kg QW

is predicted to be ~30 days.

• ALX148 PK profile (10 mg/kg QW)

is not impacted by combination drugs.

ALX148 Serum Levels for Cycle 1 Day 1

0 48 96 144 192 240 288 3360.1

1

10

100

1000

Hour

AL

X1

48

Se

rum

Co

nc

en

tra

tio

n (m

g/m

L)

1 mg/kg (N=4)

3 mg/kg (N=6)

10 mg/kg (N=3)

30 mg/kg (N=12)

10 mg/kg + pembrolizumab (N=33)

10 mg/kg + trastuzumab (N=11)

10 mg/kg + rituximab (N=5)

0 48 96 144 192 240 288 3360.1

1

10

100

1000

Hour

AL

X1

48

Se

rum

Co

nc

en

tra

tio

n (m

g/m

L)

1 mg/kg (N=4)

3 mg/kg (N=6)

10 mg/kg (N=3)

30 mg/kg (N=12)

10 mg/kg + pembrolizumab (N=33)

10 mg/kg + trastuzumab (N=11)

10 mg/kg + rituximab (N=5)

CD47 Target Occupancy by ALX148

• Near complete CD47 target occupancy (TO) by ALX148 is

maintained at ≥ 3 mg/kg QW across dosing interval

• 0.3 and 1 mg/kg QW show near complete target

occupancy at peak, but not at throat

0 21 42 63 84 1050

20

40

60

80

100

120

0.3 mg/kg (N=2)

1 mg/kg (N=4)

Days

TO

(C

D4+

)

CD4

0 21 42 63 84 1050

20

40

60

80

100

120

3 mg/kg (N=6)

Days

TO

(C

D4+

)

10 mg/kg (N=3)

30mg/kg (N=12)

CD4

3 mg/kg (N=6)

10 mg/kg (N=3)

30mg/kg (N=12)

0.3 mg/kg (N=2)

1 mg/kg (N=4)

ALX Oncology

NHL PROOF-OF-PRINCIPLE TRIAL

19

ALX148

demonstrated higher

response rate

at higher dosing

ALX148 in

NHL

Phase 1b NHL cohorts

Relapsed/Refractory NHL,

prior regimen with Rituxan

Treatment:

ALX148 10 or 15 mg/kg once a week (QW)+Rituxan 375 mg/m2 once a week for 4weeks, once monthlyfor 8 months

EHA 2020 Abstract EP1247

N=Response evaluable patients

Indolent = Follicular Lymphoma and Marginal Zone Lymphoma.Aggressive = Diffuse Large B-cell Lymphoma and Mantle Cell Lymphoma.ORR = Objective Response Rate.

All

Population ORR

22

Aggressive

N

7Indolent

40.9%

33.3%

57.1%

ORR

11

N

4

54.6%

42.9%

75.0%

10 mg/kg QW

7

15 mg/kg QW

15

ALX Oncology

ALX148 HAS INITIAL CLINICAL ACTIVITY ACROSS TUMOR TYPES IN MULTIPLE TRIALS

20

Population ≥2L HER2+ GC ≥2L HER2+ GC≥2L HNSCC(CPI-Naïve)

1L HNSCC ≥2L NHL

CombinationALX148 + Herceptin

+ Cyramza + paclitaxelALX148

+ HerceptinALX148

+ KeytrudaALX148 + Keytruda+ 5FU + platinum

ALX148+ Rituxan

N-evaluable 9 19 10 3 33

ORR ALX148

66%Benchmark

28%21%

ALX14840%

Benchmark15%

ALX14866%

Benchmark36%

54.6%

Benchmark regimen Cyramza + paclitaxel Single agent Keytruda Keytruda + 5FU + platinum

Solid tumor data as of June 30, 2020. NHL data as of April 1, 2020 EHA June 2020 Abstract EP1247. ORR = Objective Response Rate, CPI = checkpoint inhibitor. Ram/pac benchmark in GC from RAINBOW Ph3 trial (Wilke, Lancet Oncology, 2014); Keytruda single agent benchmark from KEYNOTE-40 Ph3 trial (Cohen, Lancet, 2018). Keytruda + chemo benchmark from KEYNOTE-48 Ph3 trial (Burtness, Lancet, 2019).

ALX Oncology

SUMMARY

21

High affinity and no effector

function is required to fully

inhibit CD47 safely

ALX148 tolerability

profile enables

combination with a wide

range of agents

Clinical proof-of-principle in

hematologic

and solid tumors

Demonstrated clinical

tolerability with anti-cancer

antibodies and

chemotherapy

ALX Oncology

ACKNOWLEDGEMENTS

22

• Stanford University scientists that originated the idea

• Current and past ALX Oncology members that brought it here

• Clinicians that believe in ALX148 potential

• Patients and their families that trust us